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Biomedical subjects

E Yang

Publications and source records attributed to E Yang.

At least 55 records · Page 3Linked to original sources
PubMed1995

Molecular analysis of 13 cases of MLL/11q23 secondary acute leukemia and identification of topoisomerase II consensus-binding sequences near the chromosomal breakpoint of a secondary leukemia with the t(4;11).

Rearrangements of the MLL (Mixed Lineage Leukemia) gene in the human 11q23 cytogenetic locus have been detected in secondary (therapy-related) acute leukemias in patients who have received topoisomerase II inhibitors for prior, independent neoplasms. The topoisomerase II inhibitors implicated in MLL/11q23 secondary leukemias all inhibit the religation step of reaction catalyzed by topoisomerase II. This results in the stabilization of a 'cleavable complex' with double-strand DNA breaks at the point of topoisomerase II binding. This raises the possibility that the cleavable complex participates in the translocation process in MLL/11q23 secondary leukemias. Here we report that the MLL/11q23 breakpoints in 13/13 patients with secondary leukemia map to the same breakpoint cluster region (bcr) noted in de novo MLL/11q23 acute leukemias and the presence of in vivo topoisomerase II inhibitor-induced cleavage sites in MLL/11q23 bcr. We have also cloned and sequenced the breakpoint from a MLL/11q23 secondary acute leukemia. This analysis revealed sequences similar to the consensus sequence for vertebrate topoisomerase II binding and cleavage close to the 11q23 and 4q21 breakpoints. These results support a role for topoisomerase II in mechanism generating translocations in MLL/11q23 secondary acute leukemia.

Acute Disease↗
PubMed1995

"Childhood" viruses as a cause of pneumonia in adults.

Respiratory viruses are a common cause of morbidity in childhood. Except in the child with immunodeficiency, the common respiratory viruses rarely pose a serious threat to life. Because infection with most of these viruses in childhood is nearly universal and usually bestows partial immunity, the "childhood respiratory viruses" are not generally thought of as being a cause of disease in adults. However, adults who work around children, who are frequently exposed to other adults and children with respiratory tract infections (as in a hospital clinic setting), or who are military recruits appear to be at risk of infection or reinfection with one of these agents. In addition, adults with immune deficiency are at a significant risk for serious infection. The risk of serious disease can be reduced by maximizing immunity with (re)immunization and optimal treatment of any underlying disorders. Tobacco smoke and respiratory irritants should be avoided and adults at risk for severe disease should avoid contact with infected children and adults as much as possible. Specific chemotherapy for viral pneumonia, when available, may reduce morbidity in selected individuals.

Adenoviridae↗
PubMed1995

[An analysis of ocular manifestations in cases with tumors of accessory nasal sinuses].

The ocular manifestations of 60 cases with tumors of accessory nasal sinuses were reported. They were proptosis, impairment of ocular movement, diplopia, decrease or loss of visual acuity, ptosis, etc. Of them, 42 patients came to the ophthalmology department first. All the patients were diagnosed by computerized tomography (CT scan) and pathological findings. Operative treatment was applied in 48 cases. 32 cases had improvement in ocular symptoms. Particular attention was paid to the analysis of the causes of the patients, ocular symptoms and signs. They are due to the close anatomical relationship between accessory nasal sinuses and the orbit and optic nerve canal. CT scan is helpful to the early diagnosis of the disease.

Adolescent↗
PubMed1994

Expression of MHC class I antigen in Morris rat hepatoma and normal liver.

Expression of major histocompatibility complex (MHC) class I antigen in Morris rat hepatoma 7777 and normal rat liver tissues was studied by immunohistochemical techniques, Western blot and radiobinding assay. It was found that hepatoma tissue displayed a pattern of enhanced MHC class I antigen expression compared with normal liver. This phenomenon may represent an uncommon pattern of MHC class I antigen expression of liver tumor. The influence of enhanced MHC class I antigen expression on the development and spread of tumors as well as the possible mechanisms of this enhancement are discussed.

Animals↗
PubMed1994

Relationship of phospholipid distribution to shape change in Ca(2+)-crenated and recovered human erythrocytes.

Echinocytosis induced by elevation of intracellular Ca2+ in human erythrocytes can be reversed by removal of the cation. Using back-extraction of radiolabeled dilauroyl phospholipid analogs which had been incorporated into the cell membrane, we examined the relationship between this reversible shape transformation and phospholipid distribution. Upon Ca2+ crenation of cells, surface exposure of phosphatidylserine and phosphatidylethanolamine was observed simultaneously with inward diffusion of phosphatidylcholine. Removal of Ca2+ allowed resequestration of exposed phosphatidylserine to the membrane inner monolayer, but randomized phosphatidylethanolamine and phosphatidylcholine were not redistributed to their original states. Both shape reversion and retranslocation of phosphatidylserine were reversibly inhibited vanadate. On the other hand, the cell shape recovery was found to be independent of membrane skeleton and phosphoinositide metabolism and was supported by ATP resynthesis only under conditions where the aminophospholipid translocator is active. Other Ca(2+)-mediated biochemical changes, such as generation of diacylglycerol and fatty acids, were found to have no effect on Ca2+ crenation or its reversal, or upon transbilayer distribution of any phospholipid. These findings suggest that Ca2+ induces phospholipid redistribution, possibly by direct interaction with the lipid bilayer and, further, that metabolic recovery from Ca2+ crenation reflects selective retransport of phosphatidylserine to the membrane inner monolayer.

Adult↗
PubMed1994

Oxidative interactions between the erythrocyte membrane and phosphatidylcholine vesicles.

Sonicated unilamellar phosphatidylcholine vesicles induce hemoglobin oxidation in erythrocytes and resealed membrane fragments (buds) at pH 5.5. No such oxidation was observed in vesicle-bud mixtures at pH 7.4, in cells or buds suspended in pH 5.5 buffer, or in cells incubated with multilamellar lipid vesicles at pH 5.5. In buds, vesicle-induced hemoglobin oxidation was accompanied by lipid peroxidation and formation of covalent high molecular weight protein aggregates. The causative relationships among the oxidative events were examined using selective antioxidants and membrane fragments in which the cytoplasmic domain of band 3 was cleaved. Protein cross-linking and lipid peroxidation were found to be independent events, but both were found only in concert with heme oxidation. Further, vesicle-induced hemoglobin oxidation was found to be correlated with quasi-stable adsorption of intact vesicles to cells; intercalation of foreign lipid into the cell bilayer was not required. The inability of multilamellar vesicles to induce these low pH oxidative effects suggests a steric limitation on this cell-vesicle association. The results suggest that membrane component reorganization and patching induced by low pH may enhance vesicle adsorption, which in turn initiates oxidative damage.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1994

Dideoxy sequencing and structural analysis of the rat insulin-like growth factor binding protein-1 gene.

Insulin-like growth factor binding protein-1 (IGFBP-1) is an important modulator of IGF bioavailability. To facilitate studies of IGFBP-1 regulation and function in rodent models, we cloned the rat IGFBP-1 gene and analyzed its structure by dideoxy sequencing. The rat IGFBP-1 gene is relatively small (approximately 5 kb) and contains 4 exons and 3 introns, similar to the human IGFBP-1 gene.

Amino Acid Sequence↗
PubMed1994

Secondary amine analogues of 3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid esters and N-norcocaine exhibit enhanced affinity for serotonin and norepinephrine transporters.

N-Norcocaine (2) and six N-nor-3 beta-(4'-substituted phenyl)tropane-2 beta-carboxylic acid esters (4a-f) were synthesized by N-demethylation of cocaine (1) and the appropriate 3 beta-(substituted phenyl)-tropane analogues (3a-f) with alpha-chloroethyl chloroformate. Radioligand binding affinities of 2 and 4a-f at the DA, 5-HT, and NE transporter were measured and compared to those of 1 and 3a-f. N-Demethylation produced relatively small effects at the DA transporter. In contrast, 4-19-fold and 2-44-fold enhanced affinity at the serotonin and norepinephrine transporter resulted from demethylation. N-Nor-3 beta-(4'-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (4d) with an IC50 = 0.36 nM showed the greatest affinity for the serotonin transporter. However, N-nor-3 beta-(4'-ethylphenyl)tropane-2 beta-carboxylic acid methyl ester (4e) showed the greatest selectivity for the serotonin transporter.

Animals↗
PubMed1994

Functional analysis of glucocorticoid and insulin response sequences in the rat insulin-like growth factor-binding protein-1 promoter.

Insulin-like growth factor-binding protein-1 (IGFBP-1) is produced by the liver and regulated by glucocorticoids and insulin at the level of gene transcription. To identify DNA sequences mediating the effects of glucocorticoids and insulin on IGFBP-1 promoter activity we created luciferase reporter gene constructs and performed transfection studies in H4IIE hepatoma cells. Initial studies confirmed that the IGFBP-1 promoter is functional when inserted in the correct orientation, but not in the reverse orientation. Dexamethasone (DEX) increased promoter activity 10-fold, and insulin reversed this effect of DEX by 85% at 8 h. The effects of DEX were abolished when constructs were truncated to 89 bases from the RNA cap site, and DNase footprinting with the DNA-binding domain of the human glucocorticoid receptor identified an imperfect palindrome containing two receptor-binding sites separated by three nucleotides typical of a glucocorticoid response element (GRE) at this location. Mutation of either binding site (or half-site) disrupted the effects of DEX, confirming that this sequence functions as a GRE. Two other regions of the promoter also footprinted with the glucocorticoid receptor protein and contained sequences consistent with glucocorticoid receptor-binding sites; however, neither of these footprints contained the full structure expected of a functional GRE, and neither mutation nor deletion of these other sequences altered the effects of DEX on promoter activity. To identify the DNA sequences required for the effects of insulin on glucocorticoid-stimulated promoter activity, we created internal deletions throughout the IGFBP-1 promoter region. Deletion of the 22-basepair (bp) sequence immediately 5' from the GRE disrupted the effect of insulin and appeared to increase basal promoter activity at least 2-fold in each of eight experiments (P < 0.001 vs. intact promoter). This region of the IGFBP-1 promoter contains a 19-bp palindrome (CAAAACAAACTTATTTTG) that overlaps the 5'-end of the GRE and is fully conserved in the human IGFBP-1 promoter. Each half of this palindrome resembles previously identified insulin response sequences, and deletion/mutation analysis suggests that each half may contribute to the effects of insulin on promoter activity. Gel shift studies confirmed that this palindrome binds H4IIE nuclear proteins. In summary, we have identified a GRE in the 5'-promoter region of the rat IGFBP-1 gene approximately 90 bp up-stream from the RNA cap site as well as a contiguous 22-bp region that plays a critical role in mediating the effects of insulin on glucocorticoid-stimulated promoter activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Collapse of intertrochanteric hip fractures fixed with sliding screws.

A retrospective analysis of postoperative fracture collapse was performed using data from 142 patients with intertrochanteric hip fractures fixed anatomically with sliding screws. Of the 142 patients, 80 had unstable, three- or four-part hip fractures. Significant collapse (as defined by strict radiographic criteria relating the height of the femoral head to the greater trochanter and by Doppelt's criteria) was seen in 26 of the unstable fractures. The degree of collapse was classified as type I (minimal), type II (moderate), and type III (severe). Average follow-up was 31 months. An in-depth clinical and radiographic analysis was performed evaluating pain, limp, abductor weakness, and leg-length discrepancy. The numerical degree of both vertical and horizontal fracture collapse was also analyzed. Of the patients with moderate or severe collapse, 93% had a poor functional result, whereas all the patients with minimal collapse remained asymptomatic. Although postoperative fracture impaction of hips fixed with sliding screws may promote early healing, a high rate of union, and a low rate of hardware failure, excessive collapse is a problem that needs to be addressed.

Aged↗
PubMed1993

Mechanism of intermembrane phosphatidylcholine transfer: effects of pH and membrane configuration.

The mechanism of phospholipid transfer between membranes has been studied as a function of the configuration and concentration of donor and recipient membranes. The study was motivated by the observation that dimyristoylphosphatidylcholine transfers from sonicated vesicles to erythrocytes at a 4-fold faster rate at pH 5.5 than at pH 7.4. It is unexpected that the solubility of phosphatidylcholine should be affected by pH changes in this range; indeed, the more hydrophilic homolog dilauroylphosphatidylcholine transfers at closely similar rates at pH 5.5 and 7.4. The behavior of the more hydrophobic lipid is not consistent with transfer solely as a monomer passing through the aqueous phase. The effects of membrane proximity on phospholipid transfer were examined in dilution experiments employing intact erythrocytes, resealed ghosts, erythrocyte membrane buds, and sonicated vesicles as both donor and recipient membranes. For both hydrophobic and less hydrophobic lipids, the kinetics of intermembrane transfer were affected significantly by dilution at constant donor:recipient ratios. The results were fit to a kinetic model containing contributions from both through-solution monomer transfer and transient collisional transfer. The model predicts that the mechanism of intermembrane transfer varies with experimental conditions such as membrane concentration, donor and acceptor membrane area, and surface curvature. Through-solution monomer transfer predominates for less hydrophobic lipids at all values of pH and membrane concentration, and for more hydrophobic lipids at very high membrane dilutions. Transient collisional transfer contributes significantly to the rate for relatively hydrophobic lipids in concentrated donor-acceptor systems, an effect that is particularly evident at pH values below 6. The size and surface configuration of donor and recipient membranes also alter the relative contributions of through-solution and collisional transfer.

Adult↗
PubMed1993

Pilon fractures: treatment with combined internal and external fixation.

The purpose of this study was to prospectively evaluate the use of limited internal fixation and the application of a hybrid external fixator (tensioned wires distally and 5.0 mm half pins proximally attached to a semicircular frame without crossing the ankle joint) in the treatment of severe distal tibia fractures. This technique involves accurate reduction and fixation of the intraarticular component through an incision based over a fracture site followed by stabilization of the metaphysis with the hybrid external fixator. We studied 26 patients 15-55 years of age who were followed for 8-36 months. All fractures were within 5 cm of the joint. Seventeen fractures were intraarticular, nine extraarticular, and six open. Eleven patients required bone grafting. The average time to healing was 4.2 months. Using clinically based criteria, there were 81% good and excellent results overall, 70.5% for the 17 intraarticular fractures, and 69% for Ruedi type III fractures. Complications included one superficial and one deep infection, one 10 degrees varus malunion, and three pin tract infections. This method yielded results comparable with previous studies while reducing the amount of soft tissue dissection necessary for the placement of large plates. Soft tissue complications were infrequent and the goals of early motion and fracture stability were not sacrificed.

Adolescent↗
PubMed1993

Genetic transfer and expression of reconstructed yeast artificial chromosomes containing normal and translocated BCL2 proto-oncogenes.

The goal of this study was to determine whether it will be feasible to study the expression of a large, human gene, such as the BCL2 proto-oncogene, by DNA transfection. The BCL2 proto-oncogene is 230 kb in size and is deregulated in tumor cells by translocation into the immunoglobulin heavy-chain locus. Yeast artificial chromosomes (YACs) containing the human BCL2 gene were altered by homologous recombination in Saccharomyces cerevisiae to yield replicas of the normal and translocated alleles. Constructions containing either allele and ranging in size from 360 to 800 kb were integrated stably into a mouse tumor line. Fifty-eight percent of the clones contained a copy of the entire YAC insert. Over 50% of these clones expressed appropriate levels of human BCL2 RNA and protein. These studies suggested that the expression of large human genes and their pathologic rearrangements can be studied by transfection techniques employing YACs propagated in S. cerevisiae.

Animals↗
PubMed1993

Presence of IgE antibodies to staphylococcal exotoxins on the skin of patients with atopic dermatitis. Evidence for a new group of allergens.

In the current study, we investigated whether Staphylococcus aureus grown from affected skin of atopic dermatitis (AD) patients secreted identifiable toxins that could act as allergens to induce IgE-mediated basophil histamine release. The secreted toxins of S. aureus grown from AD patients were identified by ELISA using antibodies specific for staphylococcal enterotoxin (SE) exfoliative toxin (ET), or toxic shock syndrome toxin (TSST-1). S. aureus isolates from 24 of 42 AD patients secreted identifiable toxins with SEA, SEB, and TSST accounting for 92% of the isolates. 32 of 56 AD sera (57%) tested contained significant levels of IgE primarily to SEA, SEB, and/or TSST. In contrast, although SEA, SEB, or TSST secreting S. aureus could be recovered from the skin of psoriasis patients, their sera did not contain IgE antitoxins. Freshly isolated basophils from 10 AD patients released 5-59% of total histamine in response to SEA, SEB, or TSST-1 but only with toxins to which patients had specific IgE. Basophils from eight other AD patients and six normal controls who had no IgE antitoxin failed to demonstrate toxin-induced basophil histamine release. Stripped basophils sensitized with three AD sera containing IgE to toxin released 15-41% of total basophil histamine only when exposed to the relevant toxin, but not to other toxins. Sensitization of basophils with AD sera lacking IgE antitoxin did not result in release of histamine to any of the toxins tested. These data indicate that a subset of patients with AD mount an IgE response to SEs that can be grown from their skin. These toxins may exacerbate AD by activating mast cells, basophils, and/or other Fc epsilon-receptor bearing cells armed with the relevant IgE antitoxin.

Allergens↗
PubMed1993

IMP-L2: an essential secreted immunoglobulin family member implicated in neural and ectodermal development in Drosophila.

The Drosophila IMP-L2 gene was identified as a 20-hydroxyecdysone-induced gene encoding a membrane-bound polysomal transcript. IMP-L2 is an apparent secreted member of the immunoglobulin superfamily. We have used deficiencies that remove the IMP-L2 gene to demonstrate that IMP-L2 is essential in Drosophila. The viability of IMP-L2 null zygotes is influenced by maternal IMP-L2. IMP-L2 null progeny from IMP-L2+ mothers exhibit a semilethal phenotype. IMP-L2 null progeny from IMP-L2 null mothers are 100% lethal. An IMP-L2 transgene completely suppresses the zygotic lethal phenotype and partially suppresses the lethality of IMP-L2 null progeny from IMP-L2 null mothers. In embryos, IMP-L2 mRNA is first expressed at the cellular blastoderm stage and continues to be expressed through subsequent development. IMP-L2 mRNA is detected in several sites including the ventral neuroectoderm, the tracheal pits, the pharynx and esophagus, and specific neuronal cell bodies. Staining of whole-mount embryos with anti-IMP-L2 antibodies shows that IMP-L2 protein is localized to specific neuronal structures late in embryogenesis. Expression of IMP-L2 protein in neuronal cells suggests a role in the normal development of the nervous system but no severe morphological abnormalities have been detected in IMP-L2 null embryos.

Amino Acid Sequence↗